Is RD3 p.Ser120= (c.360G>A) pathogenic?

RD3 p.Ser120= (c.360G>A) is classified Uncertain significance in RD3 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-05-30). Ultra-rare (popmax 0.0212%, sas); Associated with Leber congenital amaurosis 12.

What condition is associated with RD3 p.Ser120= (c.360G>A)?

RD3 p.Ser120= (c.360G>A) is associated with Leber congenital amaurosis 12 (ClinVar).

How common is RD3 p.Ser120= (c.360G>A) in the general population?

RD3 p.Ser120= (c.360G>A) is ultra-rare (popmax 0.0212%, sas) (gnomAD).

How is Leber congenital amaurosis inherited?

Typically Autosomal dominant, Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

RD3 p.Ser120=

c.360G>A · rs752609979 · VCV2173670

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0212%, sas)

Conditions

Leber congenital amaurosis 12

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
SpliceAI	Δ0.29	acceptor loss, 10 bp away · masked 0 · deltas
Constraint at this position
Conservation	phyloP -12	GERP -2.2
Overall
CADD	7.495	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0212% South Asian · 19/89,606 alleles

Filtering AF 0.0138% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0115%

Overall 0.00174% 28/1,606,362 alleles · ultra-rare exomes 23/1,454,168 · genomes 5/152,194 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0212%	4,716
African / African-American	0.00267%	37,414
Remaining individualsnot grpmax-eligible	0.00161%	62,138
European (non-Finnish)	0.00051%	196,081

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: RD3
Protein: p.Ser120=
Coding: c.360G>A
MANE Select: NM_001164688
dbSNP: rs752609979
Type: single nucleotide variant
Location: chr1:211479264 (GRCh38)
Gene constraint: LOEUF 1.116 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 80.99 · 1 PDB
Residue 120: an α-helix

Full RD3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Leber congenital amaurosis 12 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Leber congenital amaurosis (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive
Onset: Infancy, Neonatal
Prevalence: 1-9 / 100 000 (Europe)

Similar variants

RD3 c.296+1G>T Pathogenic/Likely pathogenic ★★ same condition
RD3 p.Arg38Ter Pathogenic ★★ same condition
RD3 p.Tyr60Ter Pathogenic ★★ same condition
RD3 c.-572G>A Uncertain significance ★★ same condition
RD3 c.*1277G>A Uncertain significance ★★ same condition
RD3 p.Ala135Val Uncertain significance ★★ ⚠ same condition
RD3 p.Arg15Trp Uncertain significance ★★ ⚠ same condition
RD3 p.Arg182Gln Uncertain significance ★★ ⚠ same condition

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/rd3-p-ser120 (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown